Disease relevance of AT3

• Influence of antithrombin III on coagulation and inflammation in porcine septic shock [1].
• The findings of high fibrin-fibrinogen degradation product levels and decreased antithrombin III levels, in association with decreased activity of multiple coagulation factors and thrombocytopenia, suggest that intravascular coagulation is a feature of this experimental infection [2].
• Prior to these clinical signs, initiation of a consumption coagulopathy was demonstrated with loss of antithrombin III and plasminogen activity [3].
• Treatment of porcine sepsis with high-dose antithrombin III reduces tissue edema and effusion but does not increase risk for bleeding [4].
• Inhibition of coronary restenosis by antithrombin III in atherosclerotic swine [5].

High impact information on AT3

• These mechanisms include: first, heparin enhancement of antithrombin III-dependent inhibition of factor V activation by thrombin; second, the inactivation of membrane-bound FVa by APC; and third, the proteolytic inactivation of membrane-bound factor V by APC, which is enhanced by heparin [6].
• The antithrombin III binding activity of endothelial cells decreased after preincubation with 1 mM homocysteine, cysteine, or 2-mercaptoethanol; no reduction in binding activity was observed after preincubation with the same concentration of methionine, alanine, or valine [7].
• In contrast with a marked reduction in the maximal antithrombin III binding capacity (approximately 30% of control), the radioactivity of [35S]sulfate incorporated into heparan sulfate on the cell surface was minimally (< 15%) reduced [7].
• Incubations of porcine aortic endothelial cell cultures with homocysteine reduced the amount of antithrombin III bound to the cell surface in a dose- and time-dependent fashion [7].
• These data indicate that histidine-rich glycoprotein does not interfere with the interaction of endothelial cell heparin-like compounds with antithrombin III [8].

Chemical compound and disease context of AT3

• Recipients were treated with an intravenous infusion of antithrombin III eight hourly (250 units per kg body weight), with or without low molecular weight heparin [9].

Biological context of AT3

• The platelet count, Owren's P&P (prothrombin plus factors VII and X), plasminogen, factor XIII, and antithrombin III did not change during the treatment [10].
• Another contains the structure identical to that of the above heptasulfated antithrombin III-binding site fragment but lacks the 3-O-sulfate group and therefore is a pro-form for the binding site [11].
• Transient kinetics of heparin-catalyzed protease inactivation by antithrombin III. The reaction step limiting heparin turnover in thrombin neutralization [12].
• In contrast to Ang II or NE, ET induced a shortening of the activated partial thromboplastin time (aPTT) and increase of antithrombin III levels (ATIII), fibrin monomers (FM), prekallikrein (PKK) and factor VIII activity at the beginning [13].
• Peptides with consensus sequences bound specifically to the pentasaccharide antithrombin III-binding site within heparin [14].

Anatomical context of AT3

• Characterization of an antiserum to guinea pig antithrombin III (AT III). II. Stimulation of T lymphocyte proliferation [15].
• Guinea pig macrophages pretreated with the esterase inhibitor, antithrombin III (AT III) show increased responsiveness to macrophage-activating factor (MAF) as demonstrated by their enhanced cytotoxicity for tumor cells [16].
• Unfractionated glycosaminoglycan heparin that had been prepared from porcine intestinal mucosa was examined for its capacity to bind antithrombin III using a new technique developed to quantitate that interaction [17].
• The present investigation was designed to clarify the role of vessel wall glycosaminoglycans (GAG) and plasma antithrombin III (AT III) in the inactivation and binding of thrombin by endothelium [18].
• Heparin immobilized in this way proved to be useful as an affinity carrier for the isolation of antithrombin III and heparin-binding proteins from boar seminal plasma [19].

Associations of AT3 with chemical compounds

• Histidine-rich glycoprotein does not interfere with interactions between antithrombin III and heparin-like compounds on vascular endothelial cells [8].
• Coagulation studies revealed that rAT-P significantly inhibited the rapid decrease in the functional concentrations of Antithrombin III, Factor XI, and fibrinogen [20].
• The present study demonstrates that the nonreducing trisaccharide portion of the structural variants of the antithrombin III-binding pentasaccharide sequence can be isolated in tetrasaccharides resistant to heparinase/heparitinases I and II, while the rest of the repeating region is degraded into disaccharide units [21].
• Proton nuclear Overhauser enhancement spectroscopy demonstrated the proximity of leucine and tyrosine (within the consensus sequence) to the N-acetyl moiety found primarily within the pentasaccharide antithrombin III-binding site of heparin [14].
• The iron chelator desferrioxamine significantly prevented the reduction of antithrombin III binding to LNA-treated cells [22].

Other interactions of AT3

• Furthermore, the endothelial cell-mediated acceleration of thrombin inactivation by antithrombin III was diminished by protamine sulfate, but was not affected by histidine-rich glycoprotein even at a histidine-rich glycoprotein/antithrombin III molar ratio of approximately 7:1 [8].
• The other factors, prekallikrein, kallikrein inhibitor, alpha 2-antiplasmin, prothrombin, and antithrombin-III were all released by the liver and underwent partial hepatic inactivation [23].
• The following parameters were measured: Platelets, partial thromboplastin time, prothrombin time, fibrinogen, factors V, VII, VIII, antithrombin III, and protein C. The values relative to baseline in the MAFI and AFI groups were compared with control by rank order test [24].
• Venous plasma levels of fibrinogen, von Willebrand factor, and antithrombin III were measured [25].
• There were no changes in the plasma concentrations of the natural antithrombotics [antithrombin-III (AT-III), protein S, and protein C] after CoQ10 supplementation [26].

Analytical, diagnostic and therapeutic context of AT3

• Stents coated with heparin (antithrombin III uptake, 5 pmol/stent) were placed in 7 pigs that did not receive aspirin (group 4) [27].
• The distribution of sites with high affinity for antithrombin III in [35S]heparin proteoglycans from rat skin was studied by affinity chromatography of the intact proteoglycans (Mr congruent to 1 x 10(6)) and degradation products [28].
• Heparin was fractionated by affinity chromatography on immobilized antithrombin III followed by gel filtration on Sephadex G-100 [29].
• This peptide [ATIII(123-139)] and a sequence-permuted analogue (ATIII random) showed similar conformational behavior (as analyzed by circular dichroism spectroscopy) in aqueous and organic media [30].
• Compared with the control group, a significant improvement in mean arterial pressure and systemic vascular resistance was observed in the PC and ATIII-PC groups [31].

References